XENCOR TRIAL RESULTS WEBCAST - XENCOR INC

Financial Performance:

• No specific revenue, earnings, cash flow, or debt figures disclosed; the company is in a pre-revenue biopharmaceutical development stage.
• Focus remains on clinical trial execution and capital efficiency rather than commercial financial metrics.
• Manufacturing capabilities are validated with high-titer cell banks scalable to 2,000 liters and a 60-month liquid formulation stability.

Guidance and Future Outlook:

• Pivotal Trial: A registration-enabling Phase 3 study for XMAP819 in advanced clear cell renal cell carcinoma (RCC) is planned to initiate in 2027.
• Dosing: 400 mcg/kg IV is selected as the putative Recommended Phase 3 Dose (RP3D).
• Regulatory Pathway: Aims to hold an End-of-Phase I meeting with the FDA in the first half of 2027 to discuss accelerated approval (single-arm) followed by a confirmatory study with an active control (tivozanib) for full approval.
• Market Goals: Targets a commercial launch in later-line settings (2nd/3rd line) initially, with a long-term goal to expand to frontline therapy by 2030, potentially exceeding blockbuster status.
• Pipeline Cadence: Multiple data readouts expected through 2027, including Phase 1b data for XMAB942 (ulcerative colitis) and XMAB412 (psoriasis).

Business Segments and Product Lines:

• XMAP819 (Renal Cell Carcinoma): A 2+1 T-cell engager targeting ENPP3; currently in Phase I expansion cohorts with confirmed activity in heavily pre-treated patients.
• Expansion Cohorts: Opened cohorts for papillary RCC, microsatellite-stable (MSS) colorectal cancer, and non-squamous non-small-cell lung cancer (NSCLC) contingent on ENPP3 expression.
• Partner Programs: Two Phase 3 programs active: ASP2138 (with Astellas) and Zaloridamig (with Amgen); awaiting J&J update on Pasiridamig (XNAB CD28 bispecific).
• Other Candidates: Upcoming data for XMAB942 (UC) and XMAB412 (psoriasis); Subcutaneous (SC) formulation of XMAP819 in dose escalation, with data expected in H1 2027.

Market and Competitive Landscape:

• Target Population: Addresses a high unmet need in advanced clear cell RCC, specifically patients exhausted by PD-1/PD-L1 inhibitors, VEGFR TKIs, and HIF-2α inhibitors.
• Market Size: Addressable global market for RCC estimated at over $11 billion, growing through 2030; >9,000 eligible patients annually in the US for the targeted 3rd-line setting.
• Differentiation: XMAP819 demonstrates an unprecedented 45.5% ORR in the 400 mcg/kg cohort (4th line), outperforming current monotherapy standards (tivozanib, belzutelan) and standard-of-care cabozantinib in response depth and durability.
• Platform Advantage: The 2+1 format offers superior tumor-to-normal selectivity compared to 1+1 bispecifics, potentially reducing on-target toxicities in solid tumors.

Risks and Challenges:

• Regulatory Uncertainty: Accelerated approval requires confirming survival benefits in a later-phase confirmatory trial.
• Clinical Complexity: Managing cytokine release syndrome (CRS) and transaminitis during priming phases, though manageable with pre-medications.
• Patient Heterogeneity: Efficacy in expanded cohorts (colorectal, lung) depends on ENPP3 expression levels which vary by histology.
• Competition: Must compete with existing VEGFR TKIs and emerging immunotherapies; reliance on T-cell engager class safety data for combination strategies.

Management Commentary and Tone:

• Confidence: Management expressed high optimism, characterizing the XMAP819 data as a "high watermark" for Phase 1 RCC trials.
• Strategic Focus: Emphasized the 2027 pivotal year as the catalyst for Zencore's transition to a commercial-stage company.
• Clinical Philosophy: Highlighted the strategy of using active controls (tivozanib) in trials to support robust full approval labels rather than just accelerated ones.
• Manufacturing: Stressed the robustness of the XMAP platform, citing stable drug substance and validated CDMO partnerships.

Analyst Questions and Answers:

• Accelerated Approval Requirements: Expected to require ~100 patients for safety analysis and a primary efficacy analysis focused on Objective Response Rate (ORR) lower bounds and Median Duration of Response (MDR) rather than survival endpoints for the single-arm accelerated path.
• Combination Safety: Confirmed lack of overlapping toxicity between XMAP819 and PD-1 inhibitors, citing preclinical data and experience with patients recently on checkpoint inhibitors without washout.
• Dose Selection: The 400 mcg/kg dose was chosen due to consistent safety with the 200 mcg/kg cohort and clear dose-response trends in efficacy; modeling supports it as the top of the sigmoidal curve.
• Subcutaneous (SC) Development: SC data expected in H1 2027; potential uses include Phase 3 as primary modality, IV as primary with SC as convenience, or purely as a lifecycle play.
• Reduced Monitoring: Plans to peel back overnight hospital stays during the priming phase using reduced monitoring cohorts, aligning with industry trends (e.g., Amgen's Charitab).
• Other Indications: ENPP3 expression is high in papillary RCC (>50%), and moderate in MSS colorectal and NSCLC (30-50%); expect similar tolerability profiles across these histologies.

Other Key Points:

• Clinical Data Highlights: 400 mcg/kg cohort showed 45.5% ORR, 81.8% Disease Control Rate (DCR), and median time to response of 2.7 months; responses are deepening over time.
• Safety Profile: CRS and rash primarily occur during the priming phase (first month) and diminish significantly at target doses; transaminitis is transient with 7-day median resolution. No treatment discontinuations due to transaminitis.
• Special Case: Detailed a patient with <25% ENPP3 expression who achieved a complete response and normalization of lesions within 42 weeks.
• Manufacturing: Drug product stable for 60 months in liquid formulation; scalable purification protocols allow for efficient GMP production.